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D. Bruyere et al. / Tetrahedron 60 (2004) 4007–4017
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the reaction was quenched with saturated aqueous NH4Cl
solution. The alcohol was extracted with Et2O (3£50 mL),
washed with brine (50 mL) and dried over Na2SO4. The
solvent was evaporated and the residue purified by flash
chromatography (PE/Et2O¼70:30) to give 5 as a yellow
(2.20 g, 14.7 mmol) was added. The mixture was refluxed
for 12 h and cooled to room temperature. Et2O (200 mL)
was added and the mixture was washed with a saturated
aqueous Na2S2O3 solution (2£100 mL), brine, dried over
Na2SO4 and concentrated in vacuo. The residue was purified
by flash chromatography using pure petroleum ether as
eluent to give the iodide 8 as a yellow oil (2.6 g, 92%).
1
liquid (1.71 g, 90%). H NMR (200 MHz, CDCl3) d 1.65
(1H, s), 1.75 (2H, m), 2.85 (2H, m), 4.15 (1H, m), 5.2 (2H,
m), 5.95 (1H, ddd, J¼17.2, 10.4, 6 Hz), 7.1 (1H, m), 7.25
(2H, m), 7.55 (1H, d, J¼7.7 Hz). 13C NMR (50 MHz,
CDCl3) d 32.2, 37.1, 72.6, 115.7, 124.6, 127.6, 127.8, 130.6,
133.0, 141.0, 141.3. IR (neat): 3400, 3060, 2920, 2860,
1640, 1570, 1470, 1020, 990, 920, 900 cm21. Anal. calcd
for C11H13OBr: C, 54.79; H, 5.43. Found: C, 55.20; H, 5.31.
A dispersion of 60% NaH in mineral oil (90.0 mg,
2.24 mmol) was suspended in a mixture of THF (5 mL)
and DMF (5 mL), and dimethylmalonate (282 mL,
2.47 mmol) was added dropwise. The resulting solution of
sodium malonate was added dropwise to a stirred solution of
the iodide derivative 8 (447 mg, 1.18 mmol) in THF
(7.5 mL) and DMF (7.5 mL) and the mixture was heated
overnight at 70 8C. The reaction was quenched with 5%
HCl. The malonate was extracted with Et2O (3£50 mL) and
the organic phase washed with brine (50 mL), dried and
concentrated in vacuo. The residue was purified by flash
chromatography (PE/Et2O¼80:20) to afford E1b as a
4.1.3. Ethyl (E)-7-(o-bromophenyl)hept-4-enoate (6). The
allylic alcohol 5 (1.71 g, 7.10 mmol) was refluxed with
freshly distilled triethyl orthoacetate (39 mL, 214 mmol)
and propionic acid (47 ml, 0.63 mmol) for 15 h. After
removal of triethyl orthoacetate under vacuum, the residual
oil was purified by flash chromatography (PE/Et2O¼70:30)
1
1
to give ester 6 as a yellow oil (1.76 g, 80%). H NMR
colorless oil (370 mg, 80%). H NMR (200 MHz, CDCl3)
(200 MHz, CDCl3) d 1.27 (3H, t, J¼7.2 Hz), 2.34 (6H, m),
2.78 (2H, m), 4.15 (2H, q, J¼7.2 Hz), 5.44 (1H, dt, J¼15.4,
6.3 Hz), 5.54 (1H, dt, J¼15.4, 6.3 Hz), 7.08 (1H, m), 7.25
(2H, m), 7.55 (1H, d, J¼7.7 Hz). 13C NMR (50 MHz,
CDCl3) d 14.3, 27.9, 32.6, 34.2, 36.1, 60.2, 124.4, 128.3,
127.5, 129.1, 130.2, 130.4, 132.7, 141.1, 173.1. IR (neat):
3060, 2980, 2860, 1740, 1570, 1470, 1440, 1370, 1180,
1020, 970, 750, 660 cm21. Anal. calcd for C15H19O2Br:
C, 57.81; H, 6.15; O, 10.28. Found: C, 57.96; H, 6.02; O,
10.41.
d 1.4 (2H, m), 1.95 (2H, m), 2.03 (2H, m), 2.3 (2H, m), 2.75
(2H, m), 3.36 (1H, t, J¼7 Hz), 3.75 (6H, s), 5.3–5.4 (2H, dt,
J¼15.1, 7 Hz), 7.19 (1H, m), 7.22 (2H, m), 7.53 (1H, d,
J¼7.5 Hz). 13C NMR (50 MHz, CDCl3) d 28, 32.2, 32.9,
36.4, 52.0, 52.6, 124.6, 127.4, 127.6, 129.9, 130.4, 130.6,
132.9, 141.0, 170.0. IR (neat): 3060, 2960, 2920, 2840, 1735
(broad), 1570, 1470, 1440, 1150, 1020, 970, 750 cm21
.
Anal. calcd for C18H23O4Br: C, 56.41; H, 6.05; O, 16.7.
Found: C, 56.62; H, 5.99; O, 16.9.
4.1.6. (E)-9-(2-Bromophenyl)-2-cyano-non-6-enoic acid
methyl ester (E1a). Prepared as above for compound E1b.
Colorless oil (42%). H NMR (200 MHz, CDCl3) d 1.31
(2H, m), 1.59 (2H, m), 1.88 (2H, m), 2.12 (2H, m), 2.79 (2H,
t, J¼22 Hz), 3.49 (1H, m), 3.82 (3H, s), 5.45 (2H, m), 7.09
(1H, m), 7.20 (2H, m), 7.51 (1H, d, J¼8.4 Hz). 13C NMR
(50 MHz, CDCl3) d 26.5, 29.2, 31.5, 32.7, 36.1, 38.8, 53.4,
116.4, 124.5, 127.3, 127.6, 129.5, 130.43, 130.45, 132.7,
141.1, 166.0. IR (neat): 3060, 2960, 2860, 2240, 1700, 1565,
1470, 1440, 1260, 1120, 1020, 970, 750, 650.
4.1.4. (E)-7-(o-Bromophenyl)hept-4-en-1-ol (7). A sol-
ution of ester 6 (1.88 g, 6.04 mmol) in dry Et2O (20 mL)
was added dropwise to a cold (0 8C) stirred suspension of
LAH (230 mg, 6.04 mmol) in dry Et2O (50 mL). The
mixture was stirred at room temperature for 1 h. Water
(0.230 mL), 1 N NaOH (0.230 mL) then 3 mL of water were
successively added until a precipitate appeared. The slurry
was filtered through a pad of celite and the filtrate was dried
over Na2SO4 and concentrated. The residual oil was purified
by flash chromatography using (PE/AcOEt¼90:10) to give
alcohol 7 as a yellow oil (1.24 g, 76%). 1H NMR (200 MHz,
CDCl3) d 1.38 (1H, s), 1.58 (2H, qn, J¼6.9 Hz), 2.06 (2H,
m), 2.3 (2H, m), 2.79 (2H, m), 3.61 (2H, t, J¼6.4 Hz), 5.44
(1H, dt, J¼15.4, 5.5 Hz), 5.53 (1H, dt, J¼15.4, 5.4 Hz), 7.08
(1H, m), 7.25 (2H, m), 7.55 (1H, d, J¼7.6 Hz). 13C NMR
(50 MHz, CDCl3) d 29.0, 32.4, 32.9, 36.4, 62.6, 124.6,
127.4, 127.7, 129.8, 130.60, 130.7, 132.9, 141.3. IR (neat):
3320, 3060, 2920, 2860, 1590, 1570, 1470, 1440, 1020, 970,
750, 660 cm21. Anal. calcd for C13H17OBr: C, 58.01; H,
6.37; O, 5.94. Found: C, 57.79; H, 6.26; O, 5.53.
1
4.1.7. (E)-2-[7-(2-Bromophenyl)-hept-4-enyl] malono-
nitrile (E1c). A dispersion of 60% NaH in mineral oil
(74.0 mg, 1.84 mmol) was suspended in THF (10 mL) and
cooled at 0 8C. Malononitrile (130 mg, 1.98 mmol) in THF
(10 mL) was added dropwise. The resulting solution of
sodium malononitrile was added at room temperature to a
solution of the iodide 8 (400 mg, 1.06 mmol) in THF
(10 mL). The resulting mixture was refluxed overnight in
THF. The reaction was quenched with a saturated aqueous
NH4Cl solution (20 mL). The dinitrile was extracted with
Et2O (3£50 mL) and the organic phase was washed with
brine (50 mL), dried and concentrated in vacuo. The residue
was purified by flash chromatography (PE/Et2O¼80:20) to
afford E1c as a colorless oil (172 mg, 50%). 1H NMR
(300 MHz, CDCl3) d 1.64 (2H, m), 1.89 (2H, m), 2.08 (2H,
m), 2.42 (2H, m), 2.8 (2H, m), 3.66 (1H, t, J¼7 Hz), 5.35
(1H, dt, J¼15.1, 7 Hz), 5.54 (1H, dt, J¼15.1, 7 Hz), 7–7.4
(3H, m), 7.52 (1H, d, J¼7.5 Hz). 13C (75 MHz, CDCl3) d
22.5, 26.1, 30.0, 31.0, 32.6, 35.9, 112.6, 124.4, 127.4, 127.6,
128.9, 130.5, 131.1, 132.8, 140.9. IR (neat): 3060, 2920,
2870, 2260, 1620, 1590, 1570, 1470, 1440, 1140, 1020, 970,
4.1.5. (E)-2-[7-(2-Bromophenyl)-hept-4-enyl] malonic
acid dimethyl ester (E1b). Methane sulfonyl chloride
(0.76 mL, 9.82 mmol) was added dropwise to a stirred
solution of alcohol 7 (2.00 g, 7.43 mmol) in a mixture of
CH2Cl2 (60 mL) and triethylamine (1.41 mL, 9.66 mmol).
After stirring for 2 h at 0 8C and 3 h at room temperature, the
reaction mixture was diluted with diethyl ether (150 mL)
and the mixture was washed with a saturated aqueous
NH4Cl solution (70 mL), dried and concentrated in vacuo.
The residue was dissolved in acetone and sodium iodide